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Immune landscape of tertiary lymphoid structures in hepatocellular carcinoma (HCC) treated with neoadjuvant immune checkpoint blockade

Neoadjuvant immunotherapy is thought to produce long-term remissions through induction of antitumor immune responses before removal of the primary tumor. Tertiary lymphoid structures (TLS), germinal center-like structures that can arise within tumors, may contribute to the establishment of immunolog...

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Autores principales: Shu, Daniel H., Ho, Won Jin, Kagohara, Luciane T., Girgis, Alexander, Shin, Sarah M., Danilova, Ludmila, Lee, Jae W., Sidiropoulos, Dimitrios N., Mitchell, Sarah, Munjal, Kabeer, Howe, Kathryn, Bendinelli, Kayla J., Qi, Hanfei, Mo, Guanglan, Montagne, Janelle, Leatherman, James M., Lopez-Vidal, Tamara Y., Zhu, Qingfeng, Huff, Amanda L., Yuan, Xuan, Hernandez, Alexei, Coyne, Erin M., Zaidi, Neeha, Zabransky, Daniel J., Engle, Logan L., Ogurtsova, Aleksandra, Baretti, Marina, Laheru, Daniel, Durham, Jennifer N., Wang, Hao, Anders, Robert, Jaffee, Elizabeth M., Fertig, Elana J., Yarchoan, Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614819/
https://www.ncbi.nlm.nih.gov/pubmed/37904980
http://dx.doi.org/10.1101/2023.10.16.562104
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author Shu, Daniel H.
Ho, Won Jin
Kagohara, Luciane T.
Girgis, Alexander
Shin, Sarah M.
Danilova, Ludmila
Lee, Jae W.
Sidiropoulos, Dimitrios N.
Mitchell, Sarah
Munjal, Kabeer
Howe, Kathryn
Bendinelli, Kayla J.
Qi, Hanfei
Mo, Guanglan
Montagne, Janelle
Leatherman, James M.
Lopez-Vidal, Tamara Y.
Zhu, Qingfeng
Huff, Amanda L.
Yuan, Xuan
Hernandez, Alexei
Coyne, Erin M.
Zaidi, Neeha
Zabransky, Daniel J.
Engle, Logan L.
Ogurtsova, Aleksandra
Baretti, Marina
Laheru, Daniel
Durham, Jennifer N.
Wang, Hao
Anders, Robert
Jaffee, Elizabeth M.
Fertig, Elana J.
Yarchoan, Mark
author_facet Shu, Daniel H.
Ho, Won Jin
Kagohara, Luciane T.
Girgis, Alexander
Shin, Sarah M.
Danilova, Ludmila
Lee, Jae W.
Sidiropoulos, Dimitrios N.
Mitchell, Sarah
Munjal, Kabeer
Howe, Kathryn
Bendinelli, Kayla J.
Qi, Hanfei
Mo, Guanglan
Montagne, Janelle
Leatherman, James M.
Lopez-Vidal, Tamara Y.
Zhu, Qingfeng
Huff, Amanda L.
Yuan, Xuan
Hernandez, Alexei
Coyne, Erin M.
Zaidi, Neeha
Zabransky, Daniel J.
Engle, Logan L.
Ogurtsova, Aleksandra
Baretti, Marina
Laheru, Daniel
Durham, Jennifer N.
Wang, Hao
Anders, Robert
Jaffee, Elizabeth M.
Fertig, Elana J.
Yarchoan, Mark
author_sort Shu, Daniel H.
collection PubMed
description Neoadjuvant immunotherapy is thought to produce long-term remissions through induction of antitumor immune responses before removal of the primary tumor. Tertiary lymphoid structures (TLS), germinal center-like structures that can arise within tumors, may contribute to the establishment of immunological memory in this setting, but understanding of their role remains limited. Here, we investigated the contribution of TLS to antitumor immunity in hepatocellular carcinoma (HCC) treated with neoadjuvant immunotherapy. We found that neoadjuvant immunotherapy induced the formation of TLS, which were associated with superior pathologic response, improved relapse free survival, and expansion of the intratumoral T and B cell repertoire. While TLS in viable tumor displayed a highly active mature morphology, in areas of tumor regression we identified an involuted TLS morphology, which was characterized by dispersion of the B cell follicle and persistence of a T cell zone enriched for ongoing antigen presentation and T cell-mature dendritic cell interactions. Involuted TLS showed increased expression of T cell memory markers and expansion of CD8(+) cytotoxic and tissue resident memory clonotypes. Collectively, these data reveal the circumstances of TLS dissolution and suggest a functional role for late-stage TLS as sites of T cell memory formation after elimination of viable tumor.
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spelling pubmed-106148192023-10-31 Immune landscape of tertiary lymphoid structures in hepatocellular carcinoma (HCC) treated with neoadjuvant immune checkpoint blockade Shu, Daniel H. Ho, Won Jin Kagohara, Luciane T. Girgis, Alexander Shin, Sarah M. Danilova, Ludmila Lee, Jae W. Sidiropoulos, Dimitrios N. Mitchell, Sarah Munjal, Kabeer Howe, Kathryn Bendinelli, Kayla J. Qi, Hanfei Mo, Guanglan Montagne, Janelle Leatherman, James M. Lopez-Vidal, Tamara Y. Zhu, Qingfeng Huff, Amanda L. Yuan, Xuan Hernandez, Alexei Coyne, Erin M. Zaidi, Neeha Zabransky, Daniel J. Engle, Logan L. Ogurtsova, Aleksandra Baretti, Marina Laheru, Daniel Durham, Jennifer N. Wang, Hao Anders, Robert Jaffee, Elizabeth M. Fertig, Elana J. Yarchoan, Mark bioRxiv Article Neoadjuvant immunotherapy is thought to produce long-term remissions through induction of antitumor immune responses before removal of the primary tumor. Tertiary lymphoid structures (TLS), germinal center-like structures that can arise within tumors, may contribute to the establishment of immunological memory in this setting, but understanding of their role remains limited. Here, we investigated the contribution of TLS to antitumor immunity in hepatocellular carcinoma (HCC) treated with neoadjuvant immunotherapy. We found that neoadjuvant immunotherapy induced the formation of TLS, which were associated with superior pathologic response, improved relapse free survival, and expansion of the intratumoral T and B cell repertoire. While TLS in viable tumor displayed a highly active mature morphology, in areas of tumor regression we identified an involuted TLS morphology, which was characterized by dispersion of the B cell follicle and persistence of a T cell zone enriched for ongoing antigen presentation and T cell-mature dendritic cell interactions. Involuted TLS showed increased expression of T cell memory markers and expansion of CD8(+) cytotoxic and tissue resident memory clonotypes. Collectively, these data reveal the circumstances of TLS dissolution and suggest a functional role for late-stage TLS as sites of T cell memory formation after elimination of viable tumor. Cold Spring Harbor Laboratory 2023-10-26 /pmc/articles/PMC10614819/ /pubmed/37904980 http://dx.doi.org/10.1101/2023.10.16.562104 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Shu, Daniel H.
Ho, Won Jin
Kagohara, Luciane T.
Girgis, Alexander
Shin, Sarah M.
Danilova, Ludmila
Lee, Jae W.
Sidiropoulos, Dimitrios N.
Mitchell, Sarah
Munjal, Kabeer
Howe, Kathryn
Bendinelli, Kayla J.
Qi, Hanfei
Mo, Guanglan
Montagne, Janelle
Leatherman, James M.
Lopez-Vidal, Tamara Y.
Zhu, Qingfeng
Huff, Amanda L.
Yuan, Xuan
Hernandez, Alexei
Coyne, Erin M.
Zaidi, Neeha
Zabransky, Daniel J.
Engle, Logan L.
Ogurtsova, Aleksandra
Baretti, Marina
Laheru, Daniel
Durham, Jennifer N.
Wang, Hao
Anders, Robert
Jaffee, Elizabeth M.
Fertig, Elana J.
Yarchoan, Mark
Immune landscape of tertiary lymphoid structures in hepatocellular carcinoma (HCC) treated with neoadjuvant immune checkpoint blockade
title Immune landscape of tertiary lymphoid structures in hepatocellular carcinoma (HCC) treated with neoadjuvant immune checkpoint blockade
title_full Immune landscape of tertiary lymphoid structures in hepatocellular carcinoma (HCC) treated with neoadjuvant immune checkpoint blockade
title_fullStr Immune landscape of tertiary lymphoid structures in hepatocellular carcinoma (HCC) treated with neoadjuvant immune checkpoint blockade
title_full_unstemmed Immune landscape of tertiary lymphoid structures in hepatocellular carcinoma (HCC) treated with neoadjuvant immune checkpoint blockade
title_short Immune landscape of tertiary lymphoid structures in hepatocellular carcinoma (HCC) treated with neoadjuvant immune checkpoint blockade
title_sort immune landscape of tertiary lymphoid structures in hepatocellular carcinoma (hcc) treated with neoadjuvant immune checkpoint blockade
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614819/
https://www.ncbi.nlm.nih.gov/pubmed/37904980
http://dx.doi.org/10.1101/2023.10.16.562104
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